Texila International Journal of Public Health Special Issue-2025 DOI: 10.21522/TIJPH.2013.SE.25.01.Art005 Received: 13.06.2024 Accepted: 16.09.2024 Published on: 31.01.2025 *Corresponding Author: drponnulakshmi.researchscientist@madch.edu.in Effects of Hesperidin on Histopathological and Epigenetic Changes in Streptozotocin-Induced Type-2 Diabetic Rats Vijayakumar Sakthivel 1 , Savitha Niren 2 , Krithika C 3 , Sridevi Gopathy 4 , Ealla Kranti Kiran Reddy 5 , Ponnulakshmi Rajagopal *1 1 Department of Central Research Laboratory, Meenakshi Ammal Dental College and Hospitals, Meenakshi Academy of Higher Education and Research (MAHER), Chennai-600 095, India 2 Department of Physiology, Chettinad Institute of medical science, CARE, Manami 3 Department of Oral Medicine & Radiology, Meenakshi Ammal Dental College & Hospital, Meenakshi Academy of Higher Education & Research (MAHER), Deemed to be University, Chennai- 600095, India 4 Department of Physiology, SRM Dental College, Bharathi Salai, Ramapuram, Chennai, Tamil Nadu, India 5 Department of Oral Pathology, Saveetha Dental College and Hospitals, Saveetha Institute of Medical and Technical Sciences, Saveetha University, Chennai India Abstract Chemicals have been shown to induce epigenetic changes that alter glucose metabolism genes, potentially leading to insulin resistance and increasing the risk of metabolic disorders like type 2 diabetes. This study was aimed to assess histopathological and epigenetic changes in insulin signalling molecules in STZ-induced type-2 diabetic rats and the possible therapeutic role of hesperidin. Hesperidin (100mg/kg b.wt) was administered to STZ-induced rats and assessed for its protective role and epigenetic mechanisms in the gastrocnemius muscle. Diabetic rats exhibited significant increase (p<0.05) in renal function markers such as urea (60, 140, 80, 70, and 79 mg/dL) and creatinine (0.9, 2, 1.2, 1.1, and 1.0 mg/dL), oxidative stress markers, while antioxidant enzymes such as superoxide dismutase (0.9, 0.5,0.8, 0.87 and U/mg protein) and catalase (1, 0.4,0.86, 0.92 and 1.13 U/mg protein) were markedly lower (p<0.05). Histopathological analysis revealed a decrease and disruption in muscle fibres. The mRNA expression of insulin signalling molecules PI3K (1, 0.6, 0.8, 1.1, and 1 fold) and Munc18 (1, 0.6, 0.8, 1, and 0.9) was significantly (p<0.01) reduced in diabetic groups. Epigenetic studies showed CpG island methylation in the promoter regions of GLUT4, Akt, and IR genes in diabetic rats. However, hesperidin treatment restored the detrimental changes caused by diabetogenic agent, streptozotocin. The present study concludes that hesperidin plays a central role in regulating epigenetic mechanisms of insulin signalling molecules and GLUT4 translocation in skeletal muscle and thereby protects the muscle cells. Keywords: DNA Methylation, Diabetes, Epigenetics, Hesperidin, Health and Well-Being, Insulin Signalling, Novel Methods. Introduction The pervasive sickness in the current era, diabetes is a leading cause of cardiovascular disease (CVD), a major global health concern. Oxidative stress in skeletal muscles is caused by obesity and hyperglycemia. It has had a major detrimental impact on human life and health economics, spreading to pandemic proportions around the globe. As a result, the